Non-natural nucleosides as theranostic agents

Abstract

A composition for monitoring DNA damage includes a 3-ethynyl-5-nitroindolyl-2′-deoxyribose compound or pharmaceutically acceptable salt thereof and a detectable moiety with a click-reactive functional group that is complementary to the alkyne group of the compound.

We claim: 
     
       1. A method of adding a non-standard 2′-deoxynucleotide 5′-triphosphate to DNA in cells of a subject in need thereof, comprising:
 obtaining a biological sample containing cancer cells over expressing terminal deoxynucleotidyl transferase (TdT) from the subject; and 
 treating the sample with an agent having the formula: 
 
       
         
           
           
               
               
           
         
         where R 1  is OH, monophosphate (H 2 O 3 PO— or (O 3 PO—) 2- ), diphosphate (H 3 (O 3 PO) 2 — or ((O 3 PO) 2 —) 3- ), triphosphate (H 4 (O 3 PO) 3 —, ((O 3 PO) 3 —) 4- ), or OR a , where R a  comprises at least one of a straight chain, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, arylsulfonyl, aralkylsulfonyl, amino acid residue or fatty acid residue; and 
         where R 5  is a nitro; or a pharmaceutically acceptable salt thereof; 
         administering to the cancer cells treated with the agent a detectable moiety, which includes an azide group complementary to the alkyne group of the agent and a Cu catalyst; and detecting the detectable moiety bound to the agent. 
       
     
     
       2. The method of  claim 1 , the detectable moiety comprising a fluorophore with an azide group. 
     
     
       3. The method of  claim 1 , wherein the detectable moiety is selected from the group consisting of chromophore, luminophore, fluorophore, quantum dot or nanoparticle light scattering label, electromagnetic spin label, calorimetric agent, magnetic substance, electron-rich material metal, electrochemiluminescent label, light scattering or plasmon resonant materials, and affinity tags including enzyme and substrate reporter groups. 
     
     
       4. A kit comprising:
 (i) a compound having the formula: 
 
       
         
           
           
               
               
           
         
         where R 1  is OH, monophosphate (H 2 O 3 PO— or (O 3 PO—) 2- ), diphosphate (H 3 (O 3 PO) 2 — or ((O 3 PO) 2 —) 3- ), triphosphate (H 4 (O 3 PO) 3 —, ((O 3 PO) 3 —) 4- ), or OR a , where R a  comprises at least one of a straight chain, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, arylsulfonyl, aralkylsulfonyl, amino acid residue or fatty acid residue; and 
         where R 5  is a nitro; or a pharmaceutically acceptable salt thereof; and 
         (ii) a detectable moiety with a click-reactive functional group that is complementary to the alkyne group of the compound. 
       
     
     
       5. The kit of  claim 4 , wherein the detectable moiety includes a fluorophore with an azide group. 
     
     
       6. The kit of  claim 4 , wherein the detectable moiety is selected from the group consisting of chromophore, luminophore, fluorophore, quantum dot or nanoparticle light scattering label, electromagnetic spin label, calorimetric agent, magnetic substance, electron-rich material metal, electrochemiluminescent label, light scattering or Plasmon resonant materials, and affinity tags including enzyme and substrate reporter groups.